The objective of this proposal is to evaluate the interaction of humoral immunity and cell-mediated immunity at the effector level against tumor cells. Both humoral immunity and thymus-dependent cell-mediated immunity play a role in resistance to M-MuSV induced tumors in mice. Specific antibodies from M-MuSV regressor mice can induce thymus-processed lymphocytes to be cytotoxic against tumor cells in vitro. The interaction of T cells and humoral antibody at the effector level may play a key role in regression of these tumors. We propose to evaluate the subpopulation(s) of thymocytes active against IgM and IgG sensitized MuSV tumor cells using fractionated antibody and thymocytes fractionated by isokinetic density centrifugation. We will evaluate the role of complement components in antibody-dependent cell-mediated cytoxicity (ADCC) against MuSV induced tumor cells utilizing C5 deficient mice as sources of antibodies and lymphocytes for the assays. The evaluate the involvement of soluble T cell IgG Fc receptors in the effector mechanisms against M-MuSV induced tumors, we will assay for Fc receptors released from splenic T cells of hosts which have been infected by M-MuSV. We will utilize isolated Fc receptors from T cells to determine if these receptors can potentiate ADCC against IgG sensitized tumor cells. We will evaluate the in vivo significance of ADCC in resistance to M-MuSV-MuLV induced tumors in terms of the immunoglobulin class(es), sub-populations of effector cells, influence of T cell Fc receptors and complement components. Thus, we will administer tumor cell inoculi into irradiated hosts along with fractionated antibody and fractionated subpopulations of effector cell with or without T cell Fc receptors. These assays will be performed in hosts which are either complement deficient genetically or have been rendered so. Such studies of the immunologic effector mechanisms in model tumor systems in mice may ultimately provide the basic information required to be able to manipulate the immune system in man for resistance to tumor development of specific tumor immunotherapy.